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Clean Room Overview

Comparison of FDA and EU Regulations


Kumar Gupta
Vice President, Parsons

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 1


AGENDA
ƒ Introduction
ƒ FDA Regulations
ƒ EU Regulations
ƒ NIH Guidelines for Biologics
ƒ Applications/Examples

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 2


Sources of Contamination

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 3


Need for Clean rooms

ƒ Sixties saw several incidences of contamination in


injectables resulting in deaths and injury
ƒ High level of cleanliness
¾ Injectable drugs and devices inserted into body
and implants - free of viable organisms and
“large” particles
¾ Terminal sterilization (SAL of 10-6 or higher)
¾ Aseptic processing (SAL of 10-3) requires highest
level of cleanliness
¾ Open manipulation of living organism –
microbiology labs, seed preparation for biologics
ƒ Lower level of cleanliness
¾ Oral dosage
¾ Topical drugs

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 4


Regulations don’t Tell Much
It is the experience
ƒ FDA regulations mostly describe results
to be obtained but not how to obtain
them
ƒ Regulations have terms like “suitable”,
“appropriate”, “adequate”, “satisfactory”
that require experience to interpret them
ƒ This gives industry the freedom to
improve and “leapfrog” one another in
raising the standards without FDA lifting
a finger (“c” in cGMPs always changes)
ƒ Parenterals have been the driving force
for clean rooms

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 5


History of Clean Room Regulations
ƒ The first Federal Standard 209 published in 1963
¾ Revised in 1966 (209A), 1973 (B), 1987 (C), 1988 (D) and
1992 (E), and withdrawn in 2001.
ƒ Followed by industry all over the world
ƒ UK published first “Orange Guide” (1971)
ƒ Aseptic Processing Guide in 1987, first time
describing class 100 and class100,000
ƒ EU issued more stringent GMPs in 1991
ƒ Industry followed EU GMPs and raised the bar
further
ƒ ISO standards adopted in 2001
ƒ FDA issued revised guide in 2004
mostly matching EU GMPs

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 6


0.5

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 7


Atlantic Divide

FDA
FDA
EMEA
EMEA

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 8


FDA Regulations

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 9


Current Good Manufacturing Practices
ƒ Umbrella GMPs, 21 CFR parts 210 & 211
ƒ Biologics, 21 CFR, part 600 series
ƒ Devices and Diagnostics, 21CFR, part 800 series
ƒ Electronic Batch Records and Signatures 21 CFR
part 11
ƒ ISPE Baseline Guidelines
ƒ International GMPs
ƒ FDA Guidelines for:
¾ Aseptic Processing
¾ Process Validation
ƒ FDA’s “Points to Consider”
ƒ ISO Standards

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 10


Guidelines
ƒ A guideline states principles and
practices of general applicability that are
not legal requirements but are
acceptable to the Food and Drug
Administration (FDA).
ƒ A person may rely upon this guideline
with the assurance of its acceptability to
FDA, or may follow different
procedures.
ƒ When different procedures are chosen,
burden of proof rests with that person.
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 11
FDA Regulation-21CFR Parts 210 & 211
Umbrella GMPs
ƒ PART 210--Current Good
Manufacturing Practice In
Manufacturing, Processing, Packing,
or Holding of Drugs; General (2
pages)
¾ Describes status, applicability and
definitions

ƒ PART 211--Current Good


Manufacturing Practice For Finished
Pharmaceuticals for administration
to humans or animals (20 pages)
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 12
FDA Regulations
ƒ 211.42 Design and construction
features (c)
• (10) Aseptic processing, which includes
as appropriate:
– (i) Floors, walls, and ceilings of
smooth, hard surfaces that are easily
cleanable
– (ii) Temperature and humidity
controls

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 13


FDA Regulations
ƒ 211.42 Design and construction features
(cont.)
– (iii) An air supply filtered through high-
efficiency particulate air filters (HEPA)
under positive pressure, regardless of
whether flow is laminar or non-laminar
– (iv) Monitoring environmental conditions
– (v) Cleaning and disinfecting the room
and equipment
– (vi) System to maintain equipment used to
control aseptic conditions
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 14
FDA Regulations
ƒ 211.44 Lighting
• Adequate lighting shall be provided in all
areas
ƒ 211.46 Ventilation, air filtration, air
heating and cooling
¾(a) Adequate ventilation shall be provided
¾(b) Control of air pressure, micro-
organisms, dust, humidity, and
temperature when appropriate

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 15


FDA Regulations
ƒ 211.46 Ventilation, air filtration, air heating and
cooling
¾(c) Pre-filters and HEPAs in air supply. For re-
circulated systems, adequate exhaust systems
or other systems adequate to control
contaminants
¾(d) Separate HVAC for
manufacture, processing,
and packing of penicillin

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 16


Summary of Clean Room Regulations

ƒ Specification and control of the following:


¾Air quality – particle count (viable and
nonviable)
¾Temperature
¾Humidity
¾Room pressurization
¾Air velocity or air changes
¾Directional flow pattern
¾Lighting
¾Room finishes

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 17


FDA Classifications Guideline (Sept. 2004)

FDA Classification (0.5 ISO EU Class Particles/m3 = 0.5 Microbiological Settling Plates
micron particles/ft3) Designation micron or larger Active Air Action Action Levels
(In Operation) levels (cfu/m3) (diam. 90mm; cfu/4
hours

100 5 Grade 3,520 1 1


A
All classifications during period of activity
1,000 6 35,200 7 3

10,000 7 Grade 352,000 10 5


B
100,000 8 Grade 3,520,000 100 50
C

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 18


Down flow Laminar Concept

Contamination moves towards the floor


Class 100 achievable throughout the room
This concept is most widely used in the pharmaceutical industry

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 19


Cross Flow Laminar Concept

Contamination moves from one wall to the other wall


Cleanest work area in the beginning
Suitable where work area is near the supply wall and a
large number of people present

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 20


Class 100,000 Clean Rooms
ƒ No more than 100,000 particles/cubic foot of
air
ƒ Particle size: 0.5 microns or larger
ƒ Air circulation rate: 20 room
volumes/hour(min)
ƒ Temperature: 72°F ±5°F or as required
ƒ Relative humidity: 30% to 50%
ƒ Differential pressure: 0.05” of water (12.5
pascals)
ƒ Bio-burden: 100 CFU/M3 (action level)
Note: Regulation requires temperature and humidity
control. However, no limits specified.

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 21


Class 100 Clean Rooms

ƒ No more than 100 particles/cubic foot of air


ƒ Particle size: 0.5 micron or larger
ƒ Temperature: 72°F ±5°F or as required
ƒ Relative humidity: 30% to 50%
ƒ Differential pressure: 0.05” of water(12.5
pascals)
ƒ Terminal HEPA filter
ƒ Laminar flow (undisturbed flow)
ƒ Air velocity: 90 ft. ±18 ft./minute (1987 guide)
ƒ Bio-burden: 1 CFU/M3 (action level)
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 22
Laminar Flow Rooms

ƒ Undisturbed flow of air in a single direction


(parallel flow lines)
ƒ Flow can be ceiling to floor (down flow) or
across parallel walls (cross flow)
ƒ Air supplied by whole ceiling or whole wall
and returned through air walls
ƒ Only empty room approaches laminar
condition
ƒ Air velocity of 90 fpm (0.45m/s) For a room
height of 9 feet = 600 air changes/hour

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 23


Typical “Class 100” Clean Room

9ft

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 24


Clean Room Monitoring
ƒ Written monitoring program - sampling location, frequency
and timing
ƒ Sampling and testing includes air quality, floors, walls and
equipment surfaces
ƒ Settling plates (Petri type dishes containing nutrient agar)
in critical areas
ƒ “Active” samplers e.g. slit to agar,
centrifugal, liquid impingement
and membrane filtration
ƒ For surfaces, touch plates, swabs,
and contact plates
ƒ Test as a minimum once daily or once
a shift while in active use, normally
more frequently or after every upset
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 25
ISO/TC209 Standard
Adopted by FDA to Replace FS 209E
Number Short Title Approved for DIS
Circulation

ISO 14644-1 Air Cleanliness Classification 3/96

ISO 14644-2 Specification for testing clean rooms to prove continued 4/97
compliance with ISO14644-1

ISO 14644-3 Metrology and test methods 4/98

ISO 14644-4 Design, construction and start-up of clean room facilities. 10/97

ISO 14644-5 Operation of clean room systems 9/98

ISO 14644-6 Isolators and transfer devices 4/99

ISO 14698-1 Bio-contamination control: General principles and measurement 10/97

ISO 14698-2 Bio-contamination control:Evaluation and interpretation of bio- 10/97


contamination data.

ISO 14698-3 Bio-contamination control: Measuring the efficiency cleaning 9/98


and disinfect ion processes of inert surfaces.

ISO 14702 Terms, definitions and units 4/99

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 26


ISO Airborne Particulate Cleanliness Classes
Maximum number of particles in each cubic meter
class equal to or greater than the specified size
0.1 µm 0.2 µm 0.3 µm 0.5 µm 1 µm 5 µm
ISO 1 10 2
4
ISO 2 100 24 10
ISO 3 1000 237 102 35 8
ISO 4 10,000 2370 1020 352 83
ISO 5 100,000 23,700 10,200 3,520 832 29
ISO 6 1,000,000 237,000 102,000 35,200 8320 293
ISO 7 352,000 83,200 2930
ISO 8 3,520,000 832,000 29,300
ISO 9 35,200,000 8,320,000 293,000

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 27


Guidance in Practice

ƒ ISO 14644 is the new US Federal Standard.


Classification should include both,ISO and
FS 209E designations
ƒ ISO 14644-1 requires
¾ ISO Class Number
¾ Specific Particle Size or Sizes
¾ Occupancy Status (as built, at rest or in
operation; FDA always requires “in operation”
Classification)

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 28


AGENDA
ƒ Introduction
ƒ FDA Regulations
ƒ EU Regulations
ƒ NIH Guidelines
for Biologics
ƒ Applications/Examples

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 29


EU Regulations
ƒ The European Economic Community (EEC)
established in 1957 by 6 nations
ƒ Today it has 27 members and
500 million people in 1.7 million sq miles
ƒ The European Commission initiates new
proposals and monitors compliance
ƒ The Pharmaceutical Committee provides
expert advice to the Commission
ƒ European Medicines Evaluation Agency
(EMEA) created in 1995 and located in
London coordinates new licensing system

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 30


EU Regulations
ƒ Directive 65/65/EEC set EC-wide
requirements for medicine control and still
remains the basis of control
ƒ Directive 89/342/EEC for vaccines
ƒ Directive 89/381/EEC for blood products
ƒ Directive 89/343/EEC for radio-
pharmaceuticals
ƒ Directive 91/356/EEC for harmonization of
GMPs
ƒ Centralized, decentralized and single state
procedure

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 31


The rules governing medicinal products in
the European Union
Volume 4 of 9
Good Manufacturing Practices
ƒ Commission Directive 91/356/EEC of 1991, GMPs for
medicinal products for human use
ƒ Commission Directive 91/412/EEC of 1991, GMPs for
veterinary medicinal products
ƒ Relevant Annexes
• Annex 1 Manufacture of sterile drug products
• Annex 2 Manufacture of biological medicinal
products for human use
• Annex 14 Manufacture of products derived from
blood or human plasma
• Annex 18 GMPs for active pharmaceutical
ingredients

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 32


International Conference on Harmonization (ICH)
ƒ Objective was to develop guidelines acceptable to
health authorities of USA, EU, and Japan (1990)
ƒ Members
¾ FDA
¾ Pharmaceutical Research and Manufactures
Association (PhRMA)
¾ European Union (EU)
¾ European Federation of Pharmaceutical Industries
and Associations (EFPIA)
¾ Japan Ministry of Health, Labor, and Welfare
(MHLW)
¾ Japan Pharmaceutical Manufactures Association
(JPMA)

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 33


EU Clean Rooms- At Rest” and
“In Operation” Condition
ƒ In order to meet “in operations” conditions,
these areas should be designed to reach
certain specified air-cleanliness levels in the
“at rest” occupancy state.
ƒ The “at-rest” state is the condition where the
installation is installed and operational,
complete with production equipment but with
no operating personnel present. “At Rest”
condition achieved in 15 to 20 minutes after
operation ceased.
ƒ The “in-operation” state is the condition where
the installation is functioning in the defined
operating mode with the specified number of
personnel working.
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 34
Clean Room Classification (EU)
Maximum Permitted Number of Particles/m3 equal to or above

At Rest In Operation
0.5 µm 5 µm 0.5 µm 5 µm

Grade A 3,500 0 3,500 0

Grade B 3,500 0 350,000 2,000

Grade C 350,000 2,000 3,500,000 20,000

Grade D 3,500,000 20,000 Not Not


defined defined

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 35


Comparison of EC & US Clean Rooms
Maximum number of 0.5 micron or larger particles/cubic meter*

EC In Operation At Rest
Classification
EC Equivalent US EC Equivalent
US**
Grade A 3,500 100 3,500 100
Grade B 350,000 10,000 3,500 100
Grade C 3,500,000 100,000 350,000 10,000
Grade D*** N/A N/A 3,500,000 100,000

*No. of particles only, not class


Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 36
FDA and EU Differences
ƒ FDA does not have Grade D

ƒ FDA’s 2004 guide does not specify velocity for


class 100, EU does specify (0.45m/s+20%,
leftover from FDA 1987 guide)

ƒ All FDA requirements are for “in operation”

ƒ Viable count: action level for FDA vs. limit for


EU (FDA more stringent)

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 37


FDA and EU Differences
ƒ EU classification at 0.5 micron and 5 micron,
FDA only at 0.5 micron

ƒ EU sampling more specific and more


extensive, EU: air sample (0.5 and 5 micron),
settling plates, contact plates, glove print;
FDA: air sample (0.5 micron) and settling
plates

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 38


AGENDA

ƒ Introduction
ƒ FDA Regulations
ƒ EU Regulations
ƒ NIH Guidelines for
Biologics
ƒ Applications/Examples

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 39


NIH Contaminant Classifications
Guidelines
Labs Production Plants Severity Containment

BSL1 BSL1-LS Minimal Primary

BSL2 BSL2-LS Low Primary


BSL3 BSL3-LS Moderate Primary +
Secondary

BSL4 High Primary +


Secondary

Lab operations are carried in less then 10L fermentor

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 40


Basis for the Classification of Biohazardous
Agents by Risk Group (RG)

ƒ Risk Group 1 (RG1) -Agents not associated with disease in healthy


adult humans
ƒ Risk Group 2 (RG2) -Agents associated with human disease but rarely
serious and for which preventive or therapeutic interventions available
ƒ Risk Group 3 (RG3) -Agents associated with serious or lethal human
disease for which preventive or therapeutic interventions may be
available (high individual risk but low community risk)
ƒ Risk Group 4 (RG4) -Agents likely to cause serious or lethal human
disease for which preventive or therapeutic interventions are not usually
available (high individual risk and high community risk)

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 41


Basis for the Classification of Biohazardous
Agents by Risk Group (RG)
Bacterial, Fungal, Parasitic, Viruses and Prions

ƒ Risk Group 1 (RG1) –


¾ asporogenic Bacillus subtilis or Bacillus licheniformis
ƒ Risk Group 2 (RG2) –
¾ Hepatitis A, B, C, D, and E viruses
¾ Herpes viruses
¾ Measles and Mumps virus
¾ Polioviruses
ƒ Risk Group 3 (RG3) –
¾ Yellow fever virus
¾ Prions-Transmissible spongioform encephalopathies (TME) agents
¾ Human immunodeficiency virus (HIV)
ƒ Risk Group 4 (RG4) –
¾ Crimean-Congo hemorrhagic fever virus
¾ Filo viruses
¾ Ebola virus

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 42


Containment for Biologics (BSL-3)

Fresh Air
Once Exhaust
Through HEPA Filter

BSL-3 A/L
+++ ++
++ 10,000 100,000
10,000

This concept can also be used for High Potency


Compounds
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 43
NIH Containment Guidelines

Ventilation – movement of air and filtration of air


(BL3)
ƒ Exhaust air not re-circulated to other areas of facility
ƒ Recommend once through air (dedicated single-pass
exhaust system)
ƒ Discharge through HEPA filters, thermal oxidizer
ƒ A bag-in/bag-out (BIBO) filter or formaldehyde gas for
decontamination of filters
ƒ Exhaust air discharged away from supply air intakes

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 44


BL3-LS Design
General Considerations

ƒ All doors, HVAC, light fixtures etc. carefully


sealed and room leak tested
ƒ All pipe and other services through walls
welded to a plate or sealed properly
ƒ Provide spare openings and seal them for
future use to avoid temptation to make holes
ƒ Strictly control all future work in the room
ƒ Spill containment dikes and room
decontamination provision

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 45


Building Pressurization Concept
for Containment (e.g. BL3)

General Area 0.0”WG (slight +ve)

100K +++

Contained Area +
100K
++

100K +

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 46


Building Pressurization Concept
for Containment

Cleaner Contained Area

General Area 0.0”WG (slight +ve)

100K ++

Contained Area +
10K

10K +++ +

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 47


AGENDA

ƒ Introduction
ƒ FDA Regulations
ƒ EU Regulations
ƒ NIH Guidelines for
Biologics
ƒ Applications/Examples

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 48


Building Pressurization Concept

General Corridor +

Controlled Environment Area + + +100K

Highest Cleanliness Area


+ + + ++
10K

++++10K

++100K

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 49


Gowning Room

At rest level of A/L should be the same as


the at rest level of higher class i.e. class 100

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 50


Typical Biologics Unit Operations

Intracellular Products

• Raw Materials Off-CAS Cell Lysis • Salt


Buffer Solution
• Water Containment & Recovery • WFI
Off-Gas

Media Fermentation Extracellular Sterile Filling


Purification
Preparation or Cell Culture Products & Lyophilization

Containment & Waste Treatment

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 51


Parenteral Plant
W FI ACTIVE ING REDIENTS
& E XCIPIENTS F

Figure 4-1: Filling and Lyophilization Operations


STERILE
SO LUTIO N
RECEIVER
Class 100,000
PREP TANK STERILE
PREFILTER FILTER with local HEPA
0.45 m m 0.22 m m
for exposed areas
F F

POLISH ING
S S
W FI S F
FILTER
0.45 mm

G LASS VIALS CLASS 100


FRO M STERILIZING FREEZE
W ASH RINSE FILLING STOPPERING TRAYING DRYING
W AREHO USE TUNNEL

W FI & CLEAN ST EAM


CLASS 100,000
RUBBER
STO PPERS W ASHER CLASS 10,000
STERILIZER
S OR
SILICO NE S CLASS 1,000
PARTS HO T AIR
& TRAYS W ASHER O VEN

S S S
TERMINAL
CARTO NER LABELER INSPECTIO N AUTOCLAVE CAPPING

LAM INAR FLOW


CLEAN STEAM
S
W FI

CASE PALLET ST RET CH TO W AREHO USE


PACKER W RAPPER

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 52


Guidance in Practice

ƒ Terminal HEPA filters in Class 100 and


Class 10,000
ƒ Low returns in Class 100, Class 10,000 ,
gowning rooms and airlocks
ƒ In parenteral plants:
¾ With curtains and RABs, surrounding
area Class 10,000
¾ With isolators, surrounding area class
100,000
Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 53
Guidance in Practice

ƒ Sufficient air change rates to dilute particulate


Class 10,000 40 to 50 air changes
Class 100,000 20 to 25 air changes
Airlocks 60 air changes
ƒ Infiltration/Ex-filtration Allowance (consistent
with pressurization)
Single door 370 CFM
double door 520 CFM

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 54


Clean Room Construction
ƒ Stick built - more flexible, late design input
possible
ƒ Prefabricated panels - superior finishes
ƒ Prefabricated modules with HVAC system
– superior construction
– may be more expensive
– parallel construction
– great in low tech geographical areas
ƒ Modular Plant with all HVAC, piping and
equipment – similar to above

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 55


•Smooth
•Minimal ledges
•Minimal joints
•Radius corners
•Non-shedding
•Non-porous
•Resistant to growth
•Withstand repeated
cleaning/sanitization

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 56


Modular Airwall Systems

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 57


Media Makeup, Grade C

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 58


20K Bioreactor, Grade C

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 59


Chromatography Column Grade B/C

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 60


Purification Suite with UF Skids
Grade B/C

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 61


International cGMP Compliance

ƒ World is one market


ƒ All new facilities have to be world class
ƒ FDA, EU and WHO – big players
ƒ Objective is the translations of
confusing, often contradictory, and non-
specific regulations into a cost effective
facility that can be easily validated,
operated, and maintained

Clean Room Overview, NJ Chapter, Feb. 21, 2008 Slide 62

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